Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression
Spike-timing-dependent long-term depression (t-LTD) of glutamatergic layer (L)4-L2/3 synapses in developing neocortex requires activation of astrocytes by endocannabinoids (eCBs), which release glutamate onto presynaptic NMDA receptors (preNMDARs). The exact function of preNMDARs in this context is...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2022/2900875 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849404007021281280 |
|---|---|
| author | Florian B. Neubauer Rogier Min Thomas Nevian |
| author_facet | Florian B. Neubauer Rogier Min Thomas Nevian |
| author_sort | Florian B. Neubauer |
| collection | DOAJ |
| description | Spike-timing-dependent long-term depression (t-LTD) of glutamatergic layer (L)4-L2/3 synapses in developing neocortex requires activation of astrocytes by endocannabinoids (eCBs), which release glutamate onto presynaptic NMDA receptors (preNMDARs). The exact function of preNMDARs in this context is still elusive and strongly debated. To elucidate their function, we show that bath application of the eCB 2-arachidonylglycerol (2-AG) induces a preNMDAR-dependent form of chemically induced LTD (eCB-LTD) in L2/3 pyramidal neurons in the juvenile somatosensory cortex of rats. Presynaptic Ca2+ imaging from L4 spiny stellate axons revealed that action potential (AP) evoked Ca2+ transients show a preNMDAR-dependent broadening during eCB-LTD induction. However, blockade of voltage-dependent Ca2+ channels (VDCCs) did not uncover direct preNMDAR-mediated Ca2+ transients in the axon. This suggests that astrocyte-mediated glutamate release onto preNMDARs does not result in a direct Ca2+ influx, but that it instead leads to an indirect interaction with presynaptic VDCCs, boosting axonal Ca2+ influx. These results reveal one of the main remaining missing pieces in the signaling cascade of t-LTD at developing cortical synapses. |
| format | Article |
| id | doaj-art-91caf42074054e0ba50070b80a8fe7ea |
| institution | Kabale University |
| issn | 1687-5443 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-91caf42074054e0ba50070b80a8fe7ea2025-08-20T03:37:06ZengWileyNeural Plasticity1687-54432022-01-01202210.1155/2022/2900875Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term DepressionFlorian B. Neubauer0Rogier Min1Thomas Nevian2Department of PhysiologyDepartment of PhysiologyDepartment of PhysiologySpike-timing-dependent long-term depression (t-LTD) of glutamatergic layer (L)4-L2/3 synapses in developing neocortex requires activation of astrocytes by endocannabinoids (eCBs), which release glutamate onto presynaptic NMDA receptors (preNMDARs). The exact function of preNMDARs in this context is still elusive and strongly debated. To elucidate their function, we show that bath application of the eCB 2-arachidonylglycerol (2-AG) induces a preNMDAR-dependent form of chemically induced LTD (eCB-LTD) in L2/3 pyramidal neurons in the juvenile somatosensory cortex of rats. Presynaptic Ca2+ imaging from L4 spiny stellate axons revealed that action potential (AP) evoked Ca2+ transients show a preNMDAR-dependent broadening during eCB-LTD induction. However, blockade of voltage-dependent Ca2+ channels (VDCCs) did not uncover direct preNMDAR-mediated Ca2+ transients in the axon. This suggests that astrocyte-mediated glutamate release onto preNMDARs does not result in a direct Ca2+ influx, but that it instead leads to an indirect interaction with presynaptic VDCCs, boosting axonal Ca2+ influx. These results reveal one of the main remaining missing pieces in the signaling cascade of t-LTD at developing cortical synapses.http://dx.doi.org/10.1155/2022/2900875 |
| spellingShingle | Florian B. Neubauer Rogier Min Thomas Nevian Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression Neural Plasticity |
| title | Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression |
| title_full | Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression |
| title_fullStr | Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression |
| title_full_unstemmed | Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression |
| title_short | Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression |
| title_sort | presynaptic nmda receptors influence ca2 dynamics by interacting with voltage dependent calcium channels during the induction of long term depression |
| url | http://dx.doi.org/10.1155/2022/2900875 |
| work_keys_str_mv | AT florianbneubauer presynapticnmdareceptorsinfluenceca2dynamicsbyinteractingwithvoltagedependentcalciumchannelsduringtheinductionoflongtermdepression AT rogiermin presynapticnmdareceptorsinfluenceca2dynamicsbyinteractingwithvoltagedependentcalciumchannelsduringtheinductionoflongtermdepression AT thomasnevian presynapticnmdareceptorsinfluenceca2dynamicsbyinteractingwithvoltagedependentcalciumchannelsduringtheinductionoflongtermdepression |